Stimulants

Article Author:
Khashayar Farzam
Article Editor:
Abdolreza Saadabadi
Updated:
6/29/2019 2:33:22 PM
PubMed Link:
Stimulants

Indications

The term stimulants covers a broad class of drugs which increase the activity of the central nervous system. These drugs are used by a very high percentage of the general population for various reasons which include performance enhancement, medical benefits, and recreational purposes. Depending on the stimulant and jurisdiction, the drug may be legal or illegal.

Caffeine is the most commonly used stimulant in the world and is used for a combination of dietary and recreational purposes as well as performance enhancement. Other legal stimulants are generally used for performance enhancement but may also find utility for specific symptoms depending on the drug. Illegal and/or prescription stimulants carry medical purposes but are also heavily used for recreational reasons.[1] 

Medical Indications

  • Attention deficit hyperactivity disorder (ADHD)
  • Narcolepsy
  • Asthma
  • Obesity
  • Nasal and sinus congestion
  • Hypotension due to anesthesia

As the most commonly used stimulant, caffeine is found in various drinks and foods such as tea, coffee, and chocolate. It is consumed habitually in many countries around the world given its mild to moderate stimulant effects which promote alertness. Its general properties have also made it rampant among students and athletes who seek a cognitive or physical edge, respectively.  

The amphetamine class of drugs is used for medical and recreational purposes. They carry a multitude of effects that include general and cognitive performance enhancement along with euphoric effects. They also induce aphrodisiac effects in many users. ADHD treatment commonly uses a combination of dextroamphetamine and levoamphetamine, as well as pure dextroamphetamine and lisdexamfetamine. Methamphetamine is a widely trafficked and illegal drug that is used for recreational purposes. Athletes use many drugs that are related to the amphetamine class of drugs for physical performance enhancement. These drugs fall under bans by the world anti-doping agency (WADA).[2] 

The purpose of this article is to review the most commonly used stimulants, their indications, and possible short term and long term adverse effects.     

Mechanism of Action

The basis of the general mechanism of stimulants revolves around increase catecholamine levels and increased agonistic activity at adrenergic receptors. 

Caffeine

Caffeine has a unique mechanism as a stimulant as it works as an inhibitor at the adenosine receptors. Agonism at these receptors induces a sensation of drowsiness, and therefore inhibition at these receptors leads to increased energy levels. 

Caffeine also increases intraocular pressure in those affected with glaucoma.[3]

Amphetamines

The general mechanism of action of amphetamines is the induction of catecholamines, specifically norepinephrine and dopamine. These catecholamines lead to increased energy levels, euphoria, increased libido, and higher cognition.[4] 

Methylphenidate

This drug blocks the dopamine transporter (DAT) as well as the norepinephrine transporter (NET), leading to increased dopamine and norepinephrine levels with the inhibition of their reuptake.[5] 

Ephedrine

The primary mechanism of ephedrine is increased norepinephrine activity at the adrenergic receptors. Pseudoephedrine specifically works also as a nasal and sinus decongestant.[6] 

Cocaine

The induction of most of the effects of cocaine is through the blockade of the dopamine transporter protein. This results in increased dopamine levels at the synaptic cleft and hence the effects of dopamine are amplified. 

There are additional stimulants available, especially in pre-workout supplements, which have direct agonistic effects at adrenergic receptors. Examples include synephrine, which is present in many supplements and methylsynephrine which is banned by the WADA. Other known stimulants, such as 1,3-dimethlamylamine (DMAA), have lesser known pharmacologic mechanisms.[7][8]

Administration

The primary method of administration for stimulants is oral intake. Recreational administration of stimulants also occurs by intramuscular and/or intravascular injection, smoking, and intranasal administration.  

Adverse Effects

Stimulants can induce a broad range of short term and long term adverse effects. The side effect profile is dependent on numerous variables. The user's body weight, the specific stimulant used, the dose of the agent taken and tolerance are the major factors that influence adverse effect outcomes. Other factors include the use of other drugs and stimulants as well as oral intake on an empty stomach. The adverse effects of stimulants include the following[9][10][11]:

  • Decreased appetite - possible therapeutic effect in specific users
  • Anxiety
  • Jitteriness
  • Headaches
  • Weight loss
  • Insomnia
  • Psychosis
  • Pruritus
  • Paranoia
  • Sweating
  • Palpitations
  • Shortness of breath
  • Chest pain
  • Hypertension
  • Tachycardia
  • Seizures
  • Arrhythmias
  • EKG abnormalities: inappropriate sinus tachycardia, sinus arrhythmia, prolonged QT, premature ventricular contractions, ventricular tachycardia
  • Cerebrovascular event
  • Sudden cardiac death

If intranasal administration occurs, particularly with cocaine, there is a risk of nose bleeds and significant rhinorrhea. 

Other long term adverse effects from stimulant use involve increased risks of strokes and myocardial infarctions. The reasoning behind the elevated risks is believed to be multifactorial and primarily due to the cardiovascular effects of stimulants.

Contraindications

There are numerous relative contraindications to the use of stimulants. Patients with advanced arteriosclerosis should use minimal stimulants given the elevated risk of myocardial infarction, as stimulants elevate cardiac demand. Also, patients with severe hypertension will exacerbate their existing elevated high blood pressure when using stimulants and therefore should minimize their use. Untreated hyperthyroidism, glaucoma, and a recent stroke are also relative contraindications to stimulant use. Cardiac arrhythmias are also known to worsen and even result from the use of certain stimulants, and hence individuals so affected should avoid stimulant use.

Younger patients under the age of 12 and pregnant patients should avoid using stimulants. From a general perspective, some patients are highly sensitive to stimulants and should either avoid using or minimize their dose.

Toxicity

Treatment of a stimulant overdose depends on the specific agent used, the ongoing adverse effects and the potential risk for further adverse effects. The generally available options for treating stimulant toxicity are benzodiazepines, beta-blockers, antiarrhythmics medications, and antihypertensive medications. Certain medications under these classes of drugs may be contraindicated depending on the specific drug used. Benzodiazepines lower the associated anxiety of stimulant toxicity and may improve the patient's vital signs. They are also the primary option if the patient is experiencing seizures. Beta blockers are used to lower the heart rate of the patient, given that tachycardia is a very common symptom of stimulant overdose. As well, they can improve the patient's hypertensive state. Antiarrhythmic medications are generally reserved for ventricular arrhythmias that result from stimulant toxicity.

It is critical to confirm the specific drug that induces the stimulant toxicity given the potential treatment contraindications. For example, cocaine overdoses are a frequent cause of stimulant toxicity. While they induce tachycardia, chest pain, and hypertension, the use of beta blockers may potentially be cardiotoxic to a patient who has overdosed on cocaine.[12]

Enhancing Healthcare Team Outcomes

Stimulants make up a broad range of drugs, of which many find a use for recreational and performance enhancement reasons. Primary care physicians and nurse practitioners can significantly improve healthcare outcomes by educating their patients on the short term and long term effects of stimulant use. While caffeine is a relatively safe stimulant, other stimulants that are used by athletes, students, and recreational users can pose a significant health threat. It is essential to not overlook them in the social history gathering of a patient. Furthermore, pharmacists are readily accessible by patients and hence can carry out a critical role in educating the public; this is especially true on the topic of pre-workout supplements which contain various stimulants. 


References

[1] Cornelis MC, The Impact of Caffeine and Coffee on Human Health. Nutrients. 2019 Feb 16;     [PubMed PMID: 30781466]
[2] Heal DJ,Smith SL,Gosden J,Nutt DJ, Amphetamine, past and present--a pharmacological and clinical perspective. Journal of psychopharmacology (Oxford, England). 2013 Jun;     [PubMed PMID: 23539642]
[3] Nehlig A,Daval JL,Debry G, Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain research. Brain research reviews. 1992 May-Aug;     [PubMed PMID: 1356551]
[4] Calipari ES,Ferris MJ, Amphetamine mechanisms and actions at the dopamine terminal revisited. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2013 May 22;     [PubMed PMID: 23699503]
[5] Volkow ND,Fowler JS,Wang G,Ding Y,Gatley SJ, Mechanism of action of methylphenidate: insights from PET imaging studies. Journal of attention disorders. 2002;     [PubMed PMID: 12685517]
[6] Persky AM,Berry NS,Pollack GM,Brouwer KL, Modelling the cardiovascular effects of ephedrine. British journal of clinical pharmacology. 2004 May;     [PubMed PMID: 15089807]
[7] Geranium 2006;     [PubMed PMID: 30000892]
[8] Farzam K,Lakhkar AD, Adrenergic Drugs 2018 Jan;     [PubMed PMID: 30480963]
[9] Bruening AB,Perez M,Ohrt TK, Exploring weight control as motivation for illicit stimulant use. Eating behaviors. 2018 Aug;     [PubMed PMID: 29886378]
[10] Farzam K,Tivakaran VS, QT Prolonging Drugs 2018 Jan;     [PubMed PMID: 30521285]
[11] Farzam K,Richards JR, Rhythm, Premature Ventricular Contraction (PVC) 2018 Jan;     [PubMed PMID: 30422584]
[12] Lo KB,Virk HUH,Lakhter V,Ram P,Gongora C,Pressman G,Figueredo V, Clinical Outcomes After Treatment of Cocaine-Induced Chest Pain with Beta-Blockers: A Systematic Review and Meta-Analysis. The American journal of medicine. 2018 Dec 16;     [PubMed PMID: 30562494]